Dolutegravir, chemically designated (4R,12aS)—N-(2,4-difluorobenzyl)-7-hydroxy-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxamide, is a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor (INSTI) indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. The marketed finished dosage form (TIVICAY™) contains dolutegravir as its sodium salt, chemically denominated sodium (4R,12aS)-9-((2,4-difluorobenzyl)carbamoyl)-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]oxazin-7-olate, which is represented by the following general chemical formula (I):

WO 2010/068253 A1 discloses a monohydrate and an anhydrous form of dolutegravir sodium as well as a crystalline form of the free compound. Processes for the preparation of said forms are also provided in the application.
WO 2013/038407 A1 discloses amorphous dolutegravir sodium and processes for preparing the same.
Hydrates of pharmaceutical drug substances are of particular interest as they provide new opportunities for preparing novel pharmaceutical compositions with improved quality, activity and/or compliance. This is due to the fact that hydrates have different physicochemical properties compared to their anhydrous counterparts such as melting point, density, habitus, chemical and physical stability, hygroscopicity, dissolution rate, solubility, bioavailability etc., which influence the formulation process and also impact the final drug product.
If an anhydrous form is selected, phase changes during the formulation process induced by hydrate formation must be avoided. This can be particularly difficult if for example wet granulation is used with a substance that is able to form hydrates like dolutegravir sodium. Hence, a stable hydrate of dolutegravir sodium would allow to easily formulate dolutegravir sodium in a controlled manner and subsequently also facilitate storage and packaging. However, the so far known dolutegravir sodium monohydrate disclosed in WO 2010/068253 A1 shows excessive water uptake when exposed to moisture and on the other hand already dehydrates below 30% relative humidity.
Therefore, there is a need for hydrates of dolutegravir sodium with improved physicochemical properties, e.g. for hydrates which are stable over a broad humidity range, in particular for hydrates absorbing only low amounts of water at elevated humidity and on the other hand preserving their crystal structure also at dry conditions. In addition, there is a need for pharmaceutical compositions comprising these hydrates, and thus also for hydrates that allow for improved formulation of dolutegravir sodium in pharmaceutical compositions.